Emma Children's Hospital, Academic Medical Center, Pediatric Intensive Care Unit, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands.
Am J Respir Cell Mol Biol. 2010 Jun;42(6):697-705. doi: 10.1165/rcmb.2009-0100OC. Epub 2009 Jul 27.
Lower respiratory tract infection by respiratory syncytial virus (RSV) is a frequent cause of acute lung injury in young children and infants. Studies in adults and animals suggest that tumor necrosis factor receptor (TNFR) ligands may mediate lung injury by causing apoptosis of epithelial cells. The main goal of the present study was to determine whether the TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) pathway may be implicated in epithelial injury during severe RSV infection in children. We report elevated levels of soluble (s)TRAIL released by leukocytes in bronchoalveolar lavage fluid (BALF) of patients with RSV-associated respiratory failure (n = 22) as compared with mechanically ventilated patients without pulmonary illness (n = 7). Primary bronchial epithelial cells of children without pulmonary disease obtained by nonbronchoscopic cytobrushing expressed both death receptors TRAIL-R1 and -R2, and were found to be susceptible for cell death by human recombinant sTRAIL in vitro. Furthermore, BALF from a patient with RSV induced cell death in these cells, which was partly attenuated by inhibiting TRAIL signaling. These data suggest that the TRAIL pro-apoptotic pathway may contribute to lung epithelial injury in severe RSV infection in children.
呼吸道合胞病毒（RSV）引起的下呼吸道感染是导致婴幼儿急性肺损伤的常见原因。成人和动物研究表明，肿瘤坏死因子受体（TNFR）配体可能通过诱导上皮细胞凋亡而介导肺损伤。本研究的主要目的是确定 TNF 相关凋亡诱导配体（Apo2L/TRAIL）途径是否与儿童严重 RSV 感染期间的上皮损伤有关。我们报告了 22 例与 RSV 相关呼吸衰竭的患者支气管肺泡灌洗液（BALF）中白细胞释放的可溶性（s）TRAIL 水平升高，与无肺部疾病的机械通气患者（n=7）相比。通过非支气管镜细胞刷获得的无肺部疾病儿童的原代支气管上皮细胞表达死亡受体 TRAIL-R1 和 -R2，并在体外发现对人重组 sTRAIL 敏感，可导致细胞死亡。此外，BALF 中的 RSV 可诱导这些细胞死亡，而 TRAIL 信号的抑制部分减弱了这种作用。这些数据表明，TRAIL 促凋亡途径可能导致儿童严重 RSV 感染中的肺上皮损伤。
